生物学的同等性とバイオアベイラビリティのジャーナル

概要

Pharmacokinetic Study of Two Macrolide Antibiotic Oral Suspensions Using an Optimized Bioassay Procedure

Parvin Zakeri-Milani, Saeed Ghanbarzadeh, Farzaneh Lotfi poor, Morteza Milani and Hadi Valizadeh

Purpose: Erythromycin (ERY) (CAS 114-07-8) is a macrolide antibacterial with a broad and essentially bacteriostatic action and Azithromycin (AZI) (CAS 83905-01-5) is a semi-synthetic, acid stable erythromycin derivative with an expanded spectrum of activity and improved tissue pharmacokinetic characteristics relative to ERY. The aim of the present study was to develop an optimized procedure for determination of macrolide antibiotics in human serum as well as to compare the bioequivalence of two commercial brands of Erythromycin and Azithromycin Suspensions in healthy Iranian volunteers. Methods: Two brands of erythromycin ethylsuccinate and azithromycin oral suspensions were used. An equivalent 400-mg ERY suspension and 500-mg AZI suspension were given orally to each subject in two separate studies as a single dose with 200 ml of water. ERY and AZI concentrations in serum were determined using an optimized agar well diffusion technique with Sarcina lutea (Micrococcus Luteus, ATCC 9341). Results: Following administration of test and reference ERY products the mean values for Cmax (1168.5, 1115.0 ng/ml), Tmax (1.4, 1.38 hr), (4021.4, 4010.0 ngh/ml), (4852.6, 4787.4 ngh/ml) and T1/2 (3.64, 3.61hr) were obtained. For AZI mean values for Cmax (468.4, 488.1 ng/ml) ,Tmax (1.96, 2.08 hr) , (7575.4, 8046.6 ngh/ml), (7990.7,8436.7 ngh/ml) and T1/2 (24.98,25.18 hr) were reported. A two-compartment model best described the disposition of ERY and AZI after oral administration in human. The analytical method was validated in terms of linearity, accuracy and precision. The limit of quantitation for ERY and AZI were 50 and 40 ng/ml respectively. Conclusion: From the results obtained it can be concluded that the optimized method introduced in this study could be successfully applied for the evaluation of pharmacokinetic parameters of both AZI and ERY. Moreover the results revealed that test preparations were equivalent with respective innovator products in terms of rate and extent of absorption.